Impaired Crkl expression contributes to the defective DNA binding of Stat5b in nonobese diabetic mice

Diabetes
Malini LalorayaJin-Xiong She

Abstract

A point mutation in the Stat5b DNA binding domain in the nonobese diabetic (NOD) mouse was shown to have weaker DNA binding compared with the B6 Stat5b. Here, we assessed the binding ability of the mutant Stat5b in the B6 genetic background (B6.NOD-c11) and the wild-type Stat5b in the NOD background (NOD.Lc11). To our surprise, the binding ability of Stat5b is inconsistent with the presence or absence of the Stat5b mutation in these congenic mice but is correlated with the expression levels of the Crkl protein, which was coprecipitated by an anti-Stat5b antibody. Both the expression of Crkl and the Stat5b binding ability are the highest in B6.NOD-c11 and the lowest in NOD while intermediate in B6 and NOD.Lc11 mice. We demonstrated that the adapter molecule Crkl can bind Stat5b and that the Crkl protein is a Stat5b binding cofactor. More importantly, profection of Crkl recombinant protein significantly increased Stat5b binding ability and rescued the binding defect of the NOD mutant Stat5b, suggesting that Crkl is a key regulatory molecule for Stat5b binding. Therefore, the defective Crkl expression may contribute to the development of diabetes in the NOD mice by exacerbating the defective Stat5b binding ability.

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Citations

Jan 17, 2009·Biotechnology Letters·K Srinivasa BabuS Meenakshisundaram
Feb 6, 2014·PloS One·Takahiro KanaiKari C Nadeau
Feb 18, 2014·American Journal of Therapeutics·K Srinivasa BabuSankaranarayanan Meenakshisundaram
Feb 16, 2016·The Journal of Allergy and Clinical Immunology·Mauro GiacomelliRaffaele Badolato
Dec 15, 2015·American Journal of Reproductive Immunology : AJRI·Renjini A Padmanabhan, Malini Laloraya
Mar 27, 2007·Biochemical and Biophysical Research Communications·Abdoreza Davoodi-SemiromiMichael Clare-Salzler
Nov 26, 2010·MAbs·Andrea L J MarschallStefan Dübel
Jun 28, 2011·Molecular Endocrinology·Renjini Ambika PadmanabhanMalini Laloraya
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Oct 7, 2015·G3 : Genes - Genomes - Genetics·Colleen M ElsoThomas C Brodnicki

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